Collagen strands and method of treating



COLLAGEN STRANDS AND METHOD OF TREATING Leo J. Novak, Dayton, Ohio,assignor to The Commonwealth Engineering Company of Ohio, Dayton, Ohio,a corporation of Ohio No Drawing. Application December 17, 1953, SerialNo. 398,883

Claims. (Cl. 128-3355) This invention relates to collagen strands andmore particularly to collagen sutures.

According to one commercial method, sutures are usually obtained fromthe intestine of the sheep, hog or cow, preferably from the smallintestine of the sheep and from a particular layer thereof called thesubmucosa. The intestines are received from the abattoir in barrels orother containers, packed in salt or not, are re-hydrated in water andthen split lengthwise into two ribbons one of which is referred to asthe roug side, the other as the smooth side. These ribbons, after beingwashed in sodium bicarbonate water and scraped free of debris, slime andso on, are combined in multiples of 1, 2, 3 or more to form a strandconsisting of the required number of plies or submucosal ribbons, theplied strand is tanned, as-with chromium or formaldehyde, a plurality ofthe strands are spun to form a wet suture, and the suture is dried undertension and polished to the required diameter.

Collagen strands suitable for use in suturesv may also be obtained byextruding a mass of collagen fibers in suspension, or a solution ofcollagenous material, through a suitable filament-forming device into acoagulating and dehydrating bath. The filaments thus formed may bewithdrawn from the bath and, after suitable processing, finally driedunder tension. A plurality of the filaments may be twisted together toform a multi-filament thread useful as a suture or in the preparation oftwisted, plied or braided strands for other purposes.

When these plied or twisted structures are dried under tension there isa tendency for the individual plies, or for short fibers if theelemental filaments comprise a plurality of short fibers, to separateunder the stretching tension with the result that the final driedproduct may not have uniform characteristics, including strength, at allportions along its length. Uniformity is an important characteristic forsutures. The problem is complicated by the fact that the use of manyavailable bonding agents for binding the strand components togetherduring the tension-drying is not practical because such agents may notbe allowed to remain on the suture when it is used to sew an incisionand removal of such agents from the suture prior to use would requirerewetting.

The object of the present invention is to provide collagen suturescomprising strands made up of a plurality of components, as submucosalribbons or a plurality of short fibers or of filaments, bonded togetherby a bonding agent which is absorbable by humans and animals andphysiologically harmless. Other objects of the invention will appearhereinafter.

The objects of the invention are accomplished by impregnating thecollagen strands with dextran which adhesively bonds the components ofthe strand into a compact structure of indefinite length and which iscapable of accepting a uniform stretch along its length.

The dextrans are high molecular weight polysaccharides made up ofanhydroglucopyranosidic units, joined by molecular structural repeatinglinkages some of which are alpha- 1,6 and some of which are non-alpha1,6 linknited States Patent 2,748,774 Patented June 5, 1956 ages and atleast 50% of which are of the alpha- 1,6 type. They vary widely in theirphysical properties including their molecular weight, molecularstructural repeating alpha- 1,6 to non-alpha- 1,6 linkages ratios andwater sensitivity. The preferred deXtrans for the present purpose arethose which are water-soluble or water-dispersible, having a molecularweight in the range 5000 to 150x10 as determined by light scatteringmeasurements, and a molecular structural repeating alpha- 1,6 tonon-alpha- 1,6 linkages ratio of 1.9:1 to 30: 1.

DeXtrans having the aforementioned properties may be obtained in variousways. For example, they may be obtained by enzyme synthesis from sucrosein the presence or substantial absence of bacteria and cellular debris.

Thus, a suitable microorganism, such as those of the Leuconostocmesenteroides or L. dextranicum types may be cultured on asucrose-containing medium, the culture may be inoculated into asucrose-bearing nutrient medium containing appropriate inorganic saltsand nitrogenous material, and the mass may be incubated until thedextran is synthesized in maximum yield. This is so-called whole culturesynthesis or synthesis in the presence of the bacteria and cellulardebris. Or the enzyme dextransucrase may be produced in aseparate step,filtered from the culture, and the filtrate, the enzyme isolatedtherefrom, or an aqueous solution of the isolated enzyme of suitableenzyme potency may be introduced into the sucrose-bearing nutrient andthe mass held until the dextran is synthesized. This is the filteredenzyme method in which the synthesis is effected in the substantialabsence of bacteria or cellular debris.

In either process, the native dextran obtained initially, which may beprecipitated from the fermentate by the addition thereto of awater-miscible aliphatic alcohol or ketone, has a very high molecularweight calculated to be in the millions, and may be readilywater-soluble, difiicultly water-soluble or for all practical purposessubstantially insoluble in water. Thus, the native dextrans obtained bythe use of whole cultures of the microorganisms or their enzymes bearingthe Northern Regional Research Laboratory classifications Leuconostocmesenteroides B5l2, 18-1146, B-ll9, and B--ll are readily soluble inwater.

These readily water-soluble native dextrans, or native water-dispersibledextrans, may be used as such, after suitable purification, as bondingagent for the collagenous fibers or the native dextrans may be partiallyhydrolyzed to dextrans of lower molecular weight. So-called clinicaldextran, i. e., dextran which complies with the specificationsestablished by U. S. military authorities, obtained in any suitable way,as by hydrolyzing the native (usually L. m. B-512) material to amolecular weight acceptable for intravenous injection (25,000 to200,000, preferably 60,000 to 90,000) may be used and may be preferred.As is known, in the conventional production of clinical dextran, thenative dextran is hydrolyzed under appropriately controlled conditionsand the dextran of desired molecular weight is isolated from thehydrolyzate. This is usually accomplished by fractionation and, inaddition to the medium fraction desired for clinical purposes, there areobtained a low fraction of molecular weight about 5000 to 50,000 and afraction of very high average molecular weight. Any one of theseWater-soluble dextranproducts may be dissolved in Water and applied tothe collagen strand for adhesively bonding the components together andmaintaining the integrity of the strand during tension-drying thereof.The eX- truded collagenous strand or twisted or plied extrudedcollagenous filaments may be treated with anaqueous 1% to 10% by weightsolution, or dispersion of the dex tran after withdrawal from thecoagulating and dehydrating, bath and following, the usualafter-treatments, including final washing. In the case of sub mucosalribbons or plied structures comprising them, these may be treated withthe dextran solution or dispersion after withdrawal from the chrome orformaldehyde tanning bath. The dextran solution may be applied to thecollagenous strand, or to the clean, tannedsubmucosal ribbons, in anyway, as by spraying, immersion, or passage through a bath of the dextransolution. The collagenous strand or submucosal ribbons may be wound on aspool and treated thereon with the dextran solution. The collagenousstrands carrying the dextran may be passed through a drying Zone betweengodets or between a spool and a godet rotating to apply tension to thestrand as it dries. if tanned or untanned submucosal collagenouscombined ribbons or plies are treated with the dextran these plies canthen be spun and dried under tension in the usual way, and prior topolishing thereof to the desired final diameter.

The final product is a compact integral structure which is uniformthroughout its length, after polishing if neccssary, and which may beused as a surgical suture without removing the dextran from it. Thedextran, which adheres adhesively to the strand, bonds the collagenousfibrils or filaments, or the submucosal ribbons, firmly together, servesas a protective for the suture and being bland, non-toxic,non-irritating, and assimilable by humans and animals, it can beabsorbed without harmful physiological effect.

The following examples are illustrative of specific embodiments of theinvention.

Example I A collagen solution is prepared as follows: kip skin isficshcd and unhaired down to the clean corium, that lamination of theanimal hide containing the greatest proportion of collagen. The coriumis cut into strips or small pieces and these are covered with a dilutesolution of 0.05 to 0.10 N formic acid having a pH of 2-4. The corium isallowed to swell for 16 to 24 hours in the acid solution at l-30 C., sothat the swelling is effected without significant gelatine formation.The excess liquid is drained off and the swollen corium is mechanicallyshredded in a meat grinder to break down the collagen fibers to thepoint where dissolution will subsequently be facilitated. The dissolvedcollagen is separated under heating (40 C. maximum temperature) withagitation to insure complete solution of any traces of undissolvedcollagen, and then centrifuged to remove elastin, hair fragments andother insoluble matter. The solution is then filtered, as through cottonbatting pads, to obtain a filtrate comprising a clear, heavilyconcentrated solution of collagen.

A 15% solution of the pure collagen in dilute acetic acid is extrudedthrough a spinneret having orifices 0.004 mil. in diameter into acoagulating and dehydrating bath at 2030 C. and comprising a 35%saturated solution of ammonium sulfate with suffieient free ammonia tomaintain the bath at a pH of about 7.3. The thread thus formed iswithdrawn from the bath by winding it up on a spool rotating to imparttwist to the filaments and at a speed to impart a stretch thereto belowtheir breaking point. The spooled thread is washed, run off the spooland through a bath consisting of a 3% by weight solution of B-512clinical dextran, and thence passed through a drying zone in which it isheated at a temperature of 50 C., to a second spool rotating at a speedsuch that the impregnated thread is given a stretch of about 20%. Acoherent uniform suture is thus obtained. It is sterilized and packagedin a sterile, germ-proof envelope for use.

Example 11 Collagen fibers cut to a length of about 0.1 to 0.2 imetersare suspended in dilute acetic acid at room ure to obtain a fibersuspension. The susruded under pressure through an elongated spinningtube having a bore of small diameter into a coagulating bath at 25 C.and comprising 25% by weight magnesium sulfate buffered withtriethanolamine to pH 7.8. The strand or seemingly continuous filamentcomprising the multiplicity of longitudinally arrayed short fibers iswithdrawn from the bath over a rotating godet, washed, passed through a5% aqueous B 5l2 clinical dextran solution, and then through a dryingzone in which it is heated to 50 C., to a second godet rotating at aperipheral speed such that the strand is stretched 50% as it dries. Thecompact, uniform strand thus obtained, in which the fibers areadhesively bonded by the dextran, is then sterilized and packaged in asterile, germ-free glass tube for storage until it is to be used.

Example III The small intestine of sheep are hydrated in water, andsplit lengthwise into two ribbons which are washed in sodium bicarbonatewater in the usual way and scraped clean. Two of the cleaned submucosalribbons are plied together and the plied structure is tanned in aformaldehyde bath in accordance with conventional practice. These tannedtwo-ply structures are then immersed for one minute in a 5% aqueoussolution of purified native B5l2 dextran. After withdrawal from thedextran bath, the structures are spun to form a wet suture, and the wetsuture obtained is dried under tension and polished in the usual way.

The strands and twisted or plied structures may be used as surgicalsutures or they may be used as tennis string or for any other purposefor which such products are useful.

Various changes and modifications may be made in details in carrying outthe invention without departing from the spirit and scope thereof and,therefore, it is to be understood that the invention is not to belimited except as defined in the appended claims.

I claim:

1. A multi-component collagen strand the components of which are bondedtogether by dextran.

2. A multi-component collagenous surgical suture impregnated withdextran which bonds the components of the suture together.

3. A collagen strand comprisng a multiplicity of discontinuous collagenfibers bonded together by dextran.

4. A collagen strand comprisng a plurality of continuous collagenousfilaments twisted together and bonded in the twisted relation bydextran.

5. A collagen strand comprising a plurality of submucosal ribbons pliedtogether and bonded in the plied relation by dextran.

6. In the production of multi-component collagen strands, theimprovement which comprises treating the strands, prior totension-drying thereof, with a 1% to 10% by weight aqueous dispersion ofdextran, whereby the strand is impregnated with dextran and thecomponents thereof are bonded together by the dextran.

7. In the production of a collagen suture comprising a multiplicity ofshort collagen fibers, the improvement which comprises treating thestrand, in the course of its production and prior to tension-dryingthereof, with a 1% to 10% by weight aqueous dispersion of dextran,whereby the strand is impregnated with dextran and the short fibersthereof are bonded together by the dextran.

8. In the production of a collagen suture comprisng a plurality ofextruded continuous collagen filaments twisted together, the improvementwhich comprises treating the strand comprising the twisted filaments,and prior to tension-drying thereof, with a 1% to 10% by weight aqueousdispersion of dextran, whereby the strand is impregnated with thedextran and the filaments are bonded together in the twisted relation bythe dextran.

9. In the production of a collagen strand comprising cleaned, tannedsubmucosal ribbons in plied relation, the improvement which comprisestreating the ribbons prior to plying and tanning thereof, with a 1% to10% by weight aqueous dispersion of dextran, and then plying a pluralityof the ribbons together, and then spinning, tension-drying, andpolishing the plied structure, the plies of the structure being held inbonded relation by the dextran.

10. In the production of a collagen strand comprising cleaned, tannedsubmucosal ribbons in plied relation, the improvement which comprisestreating the ribbons, after plying and tanning thereof, and prior to thespinning,

tension-drying and polishing steps, With a 1% to 10% 10 A ReferencesCited in the file of this patent UNITED STATES PATENTS OTHER REFERENCESArmours Ligatures and Sutures, Published by the rmour Laboratories,Chicago, U. S. A., Feb. 7, 1939, pp. 113, pp. 3-5 relied upon.

(Copy in Div. 55.)

2. A MULTI-COMPONENT COLLAGENOUS SURGICAL SUTURE IMPREGNATED WITHDEXTRAN WHICH BONDS THE COMPONENTS OF THE SUTURE TOGETHER.